Validation of the protein kinase PfCLK3 as a multistage cross-species malarial drug target.
Resumen: The requirement for next generation anti-malarials to be both curative and transmission
blocking necessitate the identification of new druggable molecular pathways. Here we
identify a selective inhibitor to the Plasmodium falciparum protein kinase PfCLK3 which we
use in combination with chemogenetics to validate PfCLK3 as a drug target acting at
multiple parasite life stages. Consistent with a role for PfCLK3 in RNA splicing, inhibition
results in the down-regulation of >400 essential parasite genes. Inhibiting plasmodium CLK3
mediates rapid killing of asexual blood stage P. falciparum and blockade of gametocyte
development preventing transmission, as well as showing parasiticidal activity against P.
berghei and P. knowlesi. Hence, our data establishes PfCLK3 as a target with the potential to
deliver both symptomatic treatment and transmission blocking in malaria
Ficheros en el ítem
Ficheros | Tamaño | Formato | Ver |
---|---|---|---|
194352.pdf | 7.714Mb | Ver/ |
Este ítem aparece en la(s) siguiente(s) colección(ones)
- MEDICINA [816]